This project will further investigate the angiotensin/receptor interaction in a variety of smooth muscles as well as other A-II target tissues. Particular attention will be paid to the effects of mono- and divalent cations on the responsiveness or degree of tachyphylaxis of a particular smooth muscle to the hormone. A more quantitative approach to the problem of tachyphylaxis will revolve around studies on the rate of onset, rate of recovery of the phenomenon. An attempt will also be made to determine if the angiotensin molecule is altered during protracted tachyphylaxis. Cardiac muscle will also be studied. Studies are also planned to determine the electrophysiological events (via sucrose gap recording) in the smooth muscle membrane under tachyphylactic vs. non-tachyphylactic conditions. This work will also be extended to a more biochemical level with studies on binding of labeled hormone to intact or subcellular fractions of smooth muscle. In addition, effects of A-II on 45Ca++-exchange and uptake (intact muscle) or 45Ca++ binding (subcellular fractions) will also be determined. Solid-phase peptide synthesis will be used to continue the synthetic work. Work will be directed ainly toward analogs useful in the physiological and biochemical studies outlined above and toward the development of competitive and non-competitive inhibitors of converting enzyme and renin.